Time-resolved Laue crystallography, as implied by its name, can only be performed on crystalline samples. The intermolecular forces that maintain crystalline order constrain large amplitude conformational motion, and this loss of flexibility may perturb or even inhibit the function of a protein. Nonetheless, Laue crystallography stands alone in its ability to acquire near-atomic structural information on ultrafast time scales. On the other hand, X-rays can also extract structural information from molecules in solution where the full range of conformational motion is permitted. Because there is no long-range order in protein solutions, Small- and Wide-Angle-X-ray-Scattering (SAXS/WAXS) from the protein is diffuse. However, diffraction rings in the SAXS/WAXS pattern report on the size and shape of the protein. Though this structural information is not at atomic resolution, it does provide a fingerprint that can be correlated via models with the protein structure. Time-dependent changes of the SAXS/WAXS fingerprint can therefore be used to assess which models best describe the reaction pathway in solution. When we first set out to study the quaternary structure transition of hemoglobin with this technique, we observed a substantial change of the WAXS pattern at the earliest time we could measure, which suggested that the WAXS pattern is sensitive to tertiary structure changes as well as quaternary structure changes. To prove this point, we recorded time-resolved WAXS patterns following photolysis of carbon monoxymyoglobin (MbCO) and observed sizable pump-induced changes. According to X-ray structures of MbCO and deoxy Mb, the rms difference in their atomic positions is less than 0.5 . This unexpected ability to sense such small but systematic structure changes is quite encouraging, and has spurred us to continue our efforts to develop this new experimental methodology. Our efforts to further these studies at the ESRF were thwarted by a lack of beamtime. Thus, we have invested much effort over the past few years to develop the infrastructure required to pursue time-resolved X-ray scattering studies at the APS. Significantly, we have succeeded in extending our time-resolved capabilities into the SAXS region while expanding even further the accessible WAXS range. To further improve the quality of our data, we have developed a sample translation stage capable of 5G acceleration which can move the sample to a new position between X-ray pulses at a repetition frequency as high as 41 Hz. The quality of the data acquired with this infrastructure is significantly improved beyond that attained earlier at the ESRF. This improvement is quite beneficial, as the X-ray scattering signal is dominated by sources other than the protein, and the signal ascribed to time-resolved structural changes is 3 to 4 orders of magnitude weaker than the static scattering signature. To extract such small signals requires a very stable and repeatable experimental methodology, as well as sophisticated computational methods to analyze the weak scattering patterns. Feedback from this analysis has led to a major redesign of the sample holder and the data acquisition protocol. For example, our data analysis showed that temperature fluctuations of less than one degree produce a WAXS signal that is large compared to the signal due to protein structural change, and thereby compromised our ability to isolate the time-resolved contribution to the WAXS scattering signal. We have mitigated this problem by developing a new thermostated sample cell holder that provides temperature control over a broad range with very high stability. Once the thermal issues were resolved, we found that we still suffered from the radiolysis effects that arise from X-ray absorption. Radiolysis produces radicals that can combine to produce dissolved gases that eventually become supersaturated. The dissolved gas can nucleate stochastically to produce tiny gas bubbles and produce a concomitant change in the scattering pattern that overwhelms the time-resolved signal of interest. We have mitigated this problem by optimizing the rate at which sample is drawn through the sample capillary, and have updated our data acquisition protocol in a fashion that facilitates recovery and reuse of our precious samples, thereby allowing us to acquire a time-resolved data set with only about 150 uL of 50 mg/ml protein solution. Once these problems were addressed, we discovered time-dependent changes in the scattering pattern due to thermal equilibration of the X-ray detector (the readout process generates heat that warms the CCD chip and alters its background level), and developed a workaround to this problem by periodically reading the detector at the same rate as that used to acquire our time-resolved data, thereby maintaining the CCD chip at a constant temperature. With these recent innovations, we can now extract the protein contribution to the total scattering signal with near shot-noise-limited detection sensitivity. In addition to time-resolved studies of protein structure changes in solution, we have also developed the ability to record protein scattering over a broad range of temperatures, spanning from 0 to over 100C. In collaboration with the group of Dr. W. A. Eaton, we have studied the temperature-dependent radius of gyration for villin (4kD), a model system extensively used to investigate the protein folding problem. The SAXS scattering intensity scales as the square of the volume. Since this protein is quite small, its scattering power is more than 20 times weaker than that from myoglobin, making this project quite challenging. Nevertheless, we have developed an experimental protocol capable of extracting the protein signal and determining its radius of gyration, Rg as a function of temperature. Moreover, ongoing analysis of scattering patterns from a dilution series is helping to unveil the nature of protein-protein interactions.